Inhibitory effects of RRR-α-tocopheryl succinate on benzo(a)pyrene (B(a)P)-induced forestomach carcinogenesis in female mice

Wu, Kun; Shan, Yu; Zhao, Yan; Yu, Jian Wu; Liu, Bai He

doi:10.3748/wjg.v7.i1.60

Cited by 37 publications

(11 citation statements)

References 33 publications

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“…We found that VES induced apoptosis in SGC-7901 human gastric cancer cells via multiple signaling pathways, including extrinsic Fas, MAP kinase, endoplasmic reticulum (ER) stress, the couple of ER stress and unfolded protein response (UPR) (8)(9)(10)(20)(21)(22). In addition, VES enhanced DOXO anticancer efficiency via promotion of DOXO influx and suppression of MDR-1 mediated DOXO efflux (21).…”

Section: Discussionmentioning

confidence: 99%

RRR-α-tocopheryl succinate induces apoptosis in human gastric cancer cells via the NF-κB signaling pathway

et al. 2014

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Abstract.To investigate the effects of the nuclear factor (NF)-κB signaling pathway on the induction of apoptosis by vitamin E succinate (RRR-α-tocopheryl succinate; VES) in human gastric carcinoma cells. Human gastric carcinoma SGC-7901 cells were treated with temperate concentrations of VES and pyrrolidine dithiocarbamate (PDTC), an inhibitor of NF-κB. Cell viability and apoptosis were respectively estimated by methylthiazol tetrazolium (MTT) assay and the Annexin V-FITC method. Western blot analysis was used to evaluate the protein expressions of NF-κBp65 and Bcl-2 family members Bcl-2, Bax and cleavage of caspase-3, caspase-9, and poly (ADP-ribose) polymerase (PARP). The DNA-binding activity of NF-κBp65 was measured by electrophoretic mobility shift assay (EMSA). Reverse transcription and polymerase chain reaction (RT-PCR) was implemented to evaluate the transcription of inhibitor of apoptosis (IAP) genes. Apoptosis assessment showed that VES induces apoptotic cell death in human gastric carcinoma cells. In the following experiments, PDTC (100 µM) was used in cell treatment 2 h before VES. The decreased ratio of the nuclear and cytosolic NF-κBp65 protein level was induced by VES and PDTC reinforced this trend. PDTC treatment significantly enhanced the decrease of NF-κB-DNA binding activity induced by VES in human gastric SGC-7901. The decrease in protein expression of Bcl-2 as well as the increase in the protein expression of Bax were induced by VES treatment. The cleavage of caspase-9, caspase-3 and PARP was induced. There was no effect on the gene transcription of c-IAP-1, c-IAP-2, and x-linked IAP (XIAP) compared with the control group, whereas mRNA levels of survivin and the neuronal apoptosis inhibitory protein (NAIP) markedly decreased. Notably, pretreatment with PDTC reinforced all the above VES-induced effects. In conclusion, VES-induced apoptosis in SGC-7901 cells is accompanied by the inhibition of the NF-κB signaling pathway, including changes in Bcl-2 family members, cleavage of caspases and gene transcription of survivin and NAIP.

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Section: Discussionmentioning

confidence: 99%

RRR-α-tocopheryl succinate induces apoptosis in human gastric cancer cells via the NF-κB signaling pathway

et al. 2014

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“…a-TOS (100 mg/kg body weight) caused a significant reduction in the volume of human colorectal cancer xenografts [54], reduced prostate tumour burden in BALB/c nude mice fed with soybean oil [55], and increased survival of immunocompromised mice with experimental human peritoneal mesotheliomas [56]. a-TOS (200 mg/kg body weight) also suppressed the number of tumours and their volume in the benzo(a)pyreneinduced forestomach carcinoma model in female thymusbearing mice [57]. In addition, it has been reported that a-TOS suppressed colon cancer metastases into the liver and mammary tumour metastases into the lungs in nude mice [53,58], which further strengthens and extends the pros-pects for a-TOS as an anticancer drug.…”

Section: Apoptogenic Properties Of A-tosmentioning

confidence: 99%

Vitamin E analogues as mitochondria‐targeting compounds: From the bench to the bedside?

Zhao

Neužil

Wu³

2008

Molecular Nutrition Food Res

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Despite considerable effort focusing on designing and finding efficient anti-cancer drugs over the last decade, little progress has been achieved, in particular in case of highly recalcitrant malignancies. Also, since there is a trend suggesting that deaths from cancers may be more frequent than from cardiovascular diseases, it is important to look for novel efficient and selective therapeutic approaches to gradually start winning the battle with cancer. Redox-silent vitamin E analogues, epitomised by alpha-tocopheryl succinate, give some hope in the quest for drugs with such properties. Thus far, these agents have been successfully tested in experimental animals with different types of cancer, showing high efficacy against malignancies including HER2-positive breast carcinomas or malignant mesotheliomas. Further research will provide additional, necessary data to launch clinical trials, possibly in near future, translating into development of innovative anti-cancer drugs acting by targeting mitochondria selectively in cancer cells.

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“…1, 2). VES has been shown to be a potent growth inhibitor of a wide variety of cancer cell lines in vitro, as well as an effective tumor growth inhibitor in vivo (1,(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14). Recently, ␣-TEA has been shown to reduce tumor burden and lung metastasis in a syngeneic mouse mammary cancer model (2).…”

Section: Introductionmentioning

confidence: 99%

Differential Response of Human Ovarian Cancer Cells to Induction of Apoptosis by Vitamin E Succinate and Vitamin E Analogue, α-TEA

Anderson¹,

Simmons-Menchaca²,

Lawson

et al. 2004

Cancer Research

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A vitamin E derivative, vitamin E succinate (VES; RRR-␣-tocopheryl succinate), and a vitamin E analogue, 2,5,7,8-tetramethyl-2R-(4R,8R,12-trimethyltridecyl)chroman-6-yloxy acetic acid (␣-TEA), induce human breast, prostate, colon, lung, cervical, and endometrial tumor cells in culture to undergo apoptosis but not normal human mammary epithelial cells, immortalized, nontumorigenic breast cells, or normal human prostate epithelial cells. Human ovarian and cervical cancer cell lines are exceptions, with ␣-TEA exhibiting greater proapoptotic effects. Although both VES and ␣-TEA can induce A2780 and subline A2780/cp70 ovarian cancer cells to undergo DNA synthesis arrest within 24 h of treatment, only ␣-TEA is an effective inducer of apoptosis. VES or ␣-TEA treatment of cp70 cells with 5, 10, or 20 g/ml for 3 days induced 5, 6, and 19% versus 9, 36, and 71% apoptosis, respectively. Colony formation data provide additional evidence that cp70 cells are more sensitive to growth inhibition by ␣-TEA than VES. Differences in stability of the ester-linked succinate moiety of VES versus the ether-linked acetic acid moiety of ␣-TEA were demonstrated by high-performance liquid chromatography analyses that showed ␣-TEA to remain intact, whereas VES was hydrolyzed to the free phenol, RRR-␣-tocopherol. Pretreatment of cp70 cells with bis-(p-nitrophenyl) phosphate, an esterase inhibitor, before VES treatment, resulted in increased levels of intact VES and apoptosis. Taken together, these data show ␣-TEA to be a potent and stable proapoptotic agent for human ovarian tumor cells and suggest that endogenous ovarian esterases can hydrolyze the succinate moiety of VES, yielding RRR-␣-tocopherol, an ineffective apoptotic-inducing agent.

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Inhibitory effects of RRR-α-tocopheryl succinate on benzo(a)pyrene (B(a)P)-induced forestomach carcinogenesis in female mice

Abstract: VES has inhibitory effects on B(a)P-induced forestomach carcinogenesis in female mice, especially by ip and it may be a potential anti-cancer agent in vivo.

Cited by 37 publications

References 33 publications

RRR-α-tocopheryl succinate induces apoptosis in human gastric cancer cells via the NF-κB signaling pathway

RRR-α-tocopheryl succinate induces apoptosis in human gastric cancer cells via the NF-κB signaling pathway

Vitamin E analogues as mitochondria‐targeting compounds: From the bench to the bedside?

Differential Response of Human Ovarian Cancer Cells to Induction of Apoptosis by Vitamin E Succinate and Vitamin E Analogue, α-TEA

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